WO1995015155A1 - Taste masked composition containing a drug/polymer complex - Google Patents

Taste masked composition containing a drug/polymer complex Download PDF

Info

Publication number
WO1995015155A1
WO1995015155A1 PCT/EP1994/003903 EP9403903W WO9515155A1 WO 1995015155 A1 WO1995015155 A1 WO 1995015155A1 EP 9403903 W EP9403903 W EP 9403903W WO 9515155 A1 WO9515155 A1 WO 9515155A1
Authority
WO
WIPO (PCT)
Prior art keywords
chewable
taste masked
therapeutic agent
complex
polymer
Prior art date
Application number
PCT/EP1994/003903
Other languages
French (fr)
Inventor
Franco Francese
Massimo Maneschi
Diego Oldani
Original Assignee
Smithkline Beecham Farmaceutici S.P.A.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Smithkline Beecham Farmaceutici S.P.A. filed Critical Smithkline Beecham Farmaceutici S.P.A.
Priority to AU12198/95A priority Critical patent/AU693144B2/en
Priority to JP7515376A priority patent/JPH09505818A/en
Priority to NZ277238A priority patent/NZ277238A/en
Priority to EP95903281A priority patent/EP0804168A1/en
Publication of WO1995015155A1 publication Critical patent/WO1995015155A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6943—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a pill, a tablet, a lozenge or a capsule

Definitions

  • the present invention relates to therapeutic agent/polymer matrix complexes which have improved taste characteristics. Many therapeutically active substances have an unpleasant taste or cause a numbing effect when administered by mouth to a patient.
  • therapeutic agent/polymer combinations are known but the therapeutic agent is coated with the polymer.
  • the problem with such products is that they are liable to be broken when orally administered by the patient, particularly when chewed, thereby allowing the therapeutic agent to be in direct contact with the mouth, thus the taste and/or numbing sensation of the therapeutic agent is no longer effectively masked.
  • a further problem with copolymers of methacrylic acid and methyl methacrylate is that when complexed with therapeutic agents the product formed tends to be a gum.
  • dimenhydrinate is useful for treating the symptoms associated with travel sickness. Dimenhydrinate has a numbing taste.
  • a preferred formulation of dimenhydrinate is in the form of a chewing gum or a chewable tablet which means that the conventional coating techniques using polymers such as anionic copolymers based on methacrylic acid and methylmethacrylate (such as Eudragit), are ineffective in masking the numbing taste because the conventional polymer coated dimenhydrinate complex is broken down when chewed by the patient.
  • polymers such as anionic copolymers based on methacrylic acid and methylmethacrylate (such as Eudragit)
  • paroxetine Another drug, paroxetine, is useful for the treatment of depression, panic disorders and obssessive compulsive disorders.
  • Paroxetine has an unpleasant bitter taste.
  • the present invention provides a therapeutic agent/polymer complex with superior taste masking qualities and can be prepared as a powder which is more easily formulated with other excipients to form conventional formulations. Accordingly, the present invention provides a chewable taste masked formulation comprising a therapeutic agent (or drug) containing at least one basic group or atom optionally in the form of a salt which is reacted with a polymer containing at least one acidic group to form a complex.
  • a preferred therapeutic agent is dimenhydrinate or paroxetine.
  • the term "basic group or atom” is understood to mean a group capable of donating electrons. Such groups include optionally substituted amino groups or optionally substituted thio groups.
  • Suitable salts of therapeutic agents include acid addition salts which are suitably pharmaceutically acceptable salts such as the hydrochloride hemi-hydrate for paroxetine.
  • the drug comprises two active components i.e. a basic one and an acidic one in the form of a salt, such as dimenhydrinate, which is the 8-chlorotheophylline salt of diphenhydramine then the term therapeutic agent in the form of a salt extends to both of these components.
  • Suitable polymers include polymethacrylates such as Eudragit L and S which are copolymers of methacrylic acid and methyl methacrylate and have a mean molecular weight of about 135,000.
  • acidic group is understood to mean a group capable of receiving electrons such as a carboxylic acid group.
  • the complexes of therapeutic agent (including salts thereof) with polymers can be in different weight ratios.
  • the complexes are preferably in a weight ratio of therapeutic agent to polymer of 1:0.8 to 1:1.5.
  • the weight ratio is 1:1.
  • the preparation of complexes of therapeutic agents (including salts thereof) with polymers may suitably be carried out by dissolving the polymer and the therapeutic agent (including salts thereof) in suitable solvents, such as iso-propanol, ethanol or diethyl ether, optionally at elevated temperatures such as 40°C, then for example adding a precipitating solvent such as n-hexane or evaporating the solvent and triturating the residue with a suitable solvent such as acetone.
  • suitable solvent such as acetone
  • such complexes may be prepared by suspending and mixing the therapeutic agent (including salts thereof) and the polymer in water at ambient or elevated temperatures such as 25 to 60°C, preferably 50°C to 60°C, for 5 to 24 hrs.
  • the resulting complex is suitably filtered and dried.
  • Complexes of therapeutic agents (including salts thereof) and polymers may be formulated into conventional chewable dosage forms such as chewable tablets, candies, chewing gums, or soft chewable gelatin capsules using techniques generally known in the art or methods described or analogious to those described in the examples.
  • dimenhydrinate/polymer complexes may be in the form of chewing gums or chewable tablets and paroxetine/ polymer complexes may be in the form of chewable tablets or chewing gums.
  • the Complex of Dimenhydrinate and Copolymer of methacrylic acid and methyl methacrylate was obtained by stepwise dissolving 10 g of Copolymer (Eudragit L) and 10 g of dimenhydrinate in 100 ml of isopropanol, which was heated to 40°C until dissolved then 200 ml of n-hexane were added to precipitate the resulting product which was then filtered and dried.
  • the Complex of Dimenhydrinate and Copolymer of methacrylic acid and methyl methacrylate was obtained by adding 1.5 kg of Dimenhydrinate and 1.5 kg of Copolymer (Eudragit L) to 22.5 litres of water, stirring at room temperature (about 20°C) for 5 hours, heating to 50°C, stirring at 50°C for 4 hours, cooling to room temperature, stirring for 2 hours at room temperature, filtering and drying.
  • Example 3 The following were granulated and admixed in a conventional manner and formed into tablets of 150 mg (Example 3), 300 mg each (Example 4) and 600 mg each (Example 5).
  • Mint flavour (g) 12 The formulation of example No. 6 was prepared by heating the sucrose and the liquid glucose dissolved in purified water, then drying the mass obtained and dispersing in the mass the CDC and the mint flavour. The final dispersion was pressed into candies of 4 g each.
  • Milled gum base is mixed with sorbitol (ca 40% of total amount), menthol (ca 90% of total amount) and aspartame (ca 25% of total amount).
  • the blend is wetted with purified water, kneeded, granulated and then dried at about 40°C.
  • the dried granules are mixed with CDC, mint oil, magnesium stearate and the remaining amounts of sorbitol, menthol and aspartame. This final mixture is pressed into chewing gums of 1230 mg each.
  • the chewing gums can be film coated by conventional film coating procedures.
  • the formulation of the Example 11 is prepared by dissolving the gelatin and glycerol in the purified water heated to 70°C and then, after cooling to 50°C, adding the saccharin sodium, the orange flavour and the CDC. The mass obtained is continually stirred, and processed with a conventional rotary-die process, to obtain soft chewable gelatin capsules of 1850 mg each.
  • the soft gelatin capsules are then dried at 20°C and 20% relative humidity for five days.
  • Example 10 The Complex of paroxetine and Copolymer of methacrylic acid and methyl metacrylate (CPC), was obtained by mixing a solution of 3g of Copolymer (Eudragit L) in 150 ml of ethanol with a solution of 3 g of paroxetine base in 100ml of diethyl ether and stirring at room temperature for 12 hours. The solvent was then evaporated under vacuum and the residue was triturated with acetone. The precipitate was collected by suction filtration, washed with acetone and dried. The 4.6 g of CPC gave the following analytical results.
  • the Complex of paroxetine and Copolymer of methacrylic acid and methyl methacrylate was obtained by adding lOg of paroxetine hydrochloride hemihydrate, lOg of Copolimer (Eudragit L) and 2.3g of sodium hydrogen carbonate to 300 ml of water. The mixture was stirred at room temperature for 12 hours, heated to 60°C and stirred at 60°C for 12 hours. After cooling to room temperature, the precipitate was collected by suction filtration, washed with water and dried.
  • CDC and pregelatinized starch are mixed, wetted with purified water, kneeded, granulated and then dried at about 40°C.
  • the dried granules are mixed with sorbitol, lactose, saccharin sodium, ammonium glycyrrhizinate, mint dried aroma and magnesium stearate, then the final mixture is pressed into tablets of 150 mg, 300 mg or 600 mg.

Abstract

A chewable taste masked formulation comprising a therapeutic agent (or drug) containing at least one basic group or atom optionally in the form of a salt, which is reacted with a polymer containing at least one acidic group to form a complex.

Description

TASTE MASKED COMPOSITION CONTAINING A DRUG/POLYMER COMPLEX
The present invention relates to therapeutic agent/polymer matrix complexes which have improved taste characteristics. Many therapeutically active substances have an unpleasant taste or cause a numbing effect when administered by mouth to a patient.
Many therapeutic agent/polymer combinations are known but the therapeutic agent is coated with the polymer. The problem with such products is that they are liable to be broken when orally administered by the patient, particularly when chewed, thereby allowing the therapeutic agent to be in direct contact with the mouth, thus the taste and/or numbing sensation of the therapeutic agent is no longer effectively masked.
A further problem with copolymers of methacrylic acid and methyl methacrylate is that when complexed with therapeutic agents the product formed tends to be a gum.
One particular drug, dimenhydrinate, is useful for treating the symptoms associated with travel sickness. Dimenhydrinate has a numbing taste.
A preferred formulation of dimenhydrinate is in the form of a chewing gum or a chewable tablet which means that the conventional coating techniques using polymers such as anionic copolymers based on methacrylic acid and methylmethacrylate (such as Eudragit), are ineffective in masking the numbing taste because the conventional polymer coated dimenhydrinate complex is broken down when chewed by the patient.
Another drug, paroxetine, is useful for the treatment of depression, panic disorders and obssessive compulsive disorders. Paroxetine has an unpleasant bitter taste.
The present invention provides a therapeutic agent/polymer complex with superior taste masking qualities and can be prepared as a powder which is more easily formulated with other excipients to form conventional formulations. Accordingly, the present invention provides a chewable taste masked formulation comprising a therapeutic agent (or drug) containing at least one basic group or atom optionally in the form of a salt which is reacted with a polymer containing at least one acidic group to form a complex.
A preferred therapeutic agent is dimenhydrinate or paroxetine. The term "basic group or atom" is understood to mean a group capable of donating electrons. Such groups include optionally substituted amino groups or optionally substituted thio groups.
Suitable salts of therapeutic agents include acid addition salts which are suitably pharmaceutically acceptable salts such as the hydrochloride hemi-hydrate for paroxetine.
It should be appreciated that in cases where the drug comprises two active components i.e. a basic one and an acidic one in the form of a salt, such as dimenhydrinate, which is the 8-chlorotheophylline salt of diphenhydramine then the term therapeutic agent in the form of a salt extends to both of these components.
Suitable polymers include polymethacrylates such as Eudragit L and S which are copolymers of methacrylic acid and methyl methacrylate and have a mean molecular weight of about 135,000.
The term "acidic group" is understood to mean a group capable of receiving electrons such as a carboxylic acid group.
The complexes of therapeutic agent (including salts thereof) with polymers can be in different weight ratios. For paroxetine and dimenhydrinate, the complexes are preferably in a weight ratio of therapeutic agent to polymer of 1:0.8 to 1:1.5. Preferably the weight ratio is 1:1. The preparation of complexes of therapeutic agents (including salts thereof) with polymers may suitably be carried out by dissolving the polymer and the therapeutic agent (including salts thereof) in suitable solvents, such as iso-propanol, ethanol or diethyl ether, optionally at elevated temperatures such as 40°C, then for example adding a precipitating solvent such as n-hexane or evaporating the solvent and triturating the residue with a suitable solvent such as acetone. The resulting precipitated complex is suitably filtered and dried.
Alternatively, such complexes may be prepared by suspending and mixing the therapeutic agent (including salts thereof) and the polymer in water at ambient or elevated temperatures such as 25 to 60°C, preferably 50°C to 60°C, for 5 to 24 hrs. The resulting complex is suitably filtered and dried.
Complexes of therapeutic agents (including salts thereof) and polymers may be formulated into conventional chewable dosage forms such as chewable tablets, candies, chewing gums, or soft chewable gelatin capsules using techniques generally known in the art or methods described or analogious to those described in the examples.
Preferably dimenhydrinate/polymer complexes may be in the form of chewing gums or chewable tablets and paroxetine/ polymer complexes may be in the form of chewable tablets or chewing gums.
The following examples are illustrative of the present invention.
Example 1
The Complex of Dimenhydrinate and Copolymer of methacrylic acid and methyl methacrylate (CDC), was obtained by stepwise dissolving 10 g of Copolymer (Eudragit L) and 10 g of dimenhydrinate in 100 ml of isopropanol, which was heated to 40°C until dissolved then 200 ml of n-hexane were added to precipitate the resulting product which was then filtered and dried.
The 16.8 g of CDC gave the following analytical results.
Appearance white powder
Numbing taste absent
Dimenhydrinate (HPLC assay) 45.78 mg/lOO mg of CDC.
Example 2
The Complex of Dimenhydrinate and Copolymer of methacrylic acid and methyl methacrylate (CDC), was obtained by adding 1.5 kg of Dimenhydrinate and 1.5 kg of Copolymer (Eudragit L) to 22.5 litres of water, stirring at room temperature (about 20°C) for 5 hours, heating to 50°C, stirring at 50°C for 4 hours, cooling to room temperature, stirring for 2 hours at room temperature, filtering and drying.
The 2.81 kg of CDC, gave the following analytical results:
Appearance white powder
Numbing taste absent
Dimenhydrinate (HPLC assay) 46.27 mg/lOO mg of CDC
Moisture (K.F.) 0.54%
Chewable Tablets
Examples 3 - 5
The following were granulated and admixed in a conventional manner and formed into tablets of 150 mg (Example 3), 300 mg each (Example 4) and 600 mg each (Example 5).
Example No.
3 4 5
Complex of Dimenhydrinate and Copolymer of 50 100 200 methacrylic acid and methyl methacrylate (CDC)(g)
Pregelatinized starch (g) 12.5 25 50
Lactose (g) 15 30 60
Saccharin sodium (g) 10 20
Mint dry flavour (g) 10 20
Sorbitol (g) 58.5 117 234
Ammonium glycyrrhizinate (g) 1.5 3 6
Magnesium stearate (g) 2.5 5 10
Candies
Example 6
Complex of Dimenhydrinate and Copolymer of methacrylic acid 100 and methyl methacrylate (CDC) (g)
Sucrose (g) 1944
Liquid glucose (g) 1944
Mint flavour (g) 12 The formulation of example No. 6 was prepared by heating the sucrose and the liquid glucose dissolved in purified water, then drying the mass obtained and dispersing in the mass the CDC and the mint flavour. The final dispersion was pressed into candies of 4 g each.
Chewing Gums
Examples 7 & 8
Example No. 7 8
Complex of Dimenhydrinate and Copolymer of 50 100 methacrylic acid and methyl methacrylate (CDC) (g)
Gum base (g) 495 495
Sorbitol (g) 637.5 587.5
Mint oil (g) 10.7 10.7
Menthol (g) 16.5 16.5
Aspartame (g) 7.6 7.6
Magnesium stearate (g) 12.7 22.7
Milled gum base is mixed with sorbitol (ca 40% of total amount), menthol (ca 90% of total amount) and aspartame (ca 25% of total amount). The blend is wetted with purified water, kneeded, granulated and then dried at about 40°C. The dried granules are mixed with CDC, mint oil, magnesium stearate and the remaining amounts of sorbitol, menthol and aspartame. This final mixture is pressed into chewing gums of 1230 mg each. The chewing gums can be film coated by conventional film coating procedures. Soft Chewable Gelatin Capsule
Example 9
Complex of Dimenhydrinate and Copolymer of methacrylic acid 100 and methyl methacrylate (CDC) (g)
Gelatin (g) 900
Glycerol (g) 345
Saccharin sodium (g) 5
Orange flavour (g) 50
Purified water (g) 450
The formulation of the Example 11 is prepared by dissolving the gelatin and glycerol in the purified water heated to 70°C and then, after cooling to 50°C, adding the saccharin sodium, the orange flavour and the CDC. The mass obtained is continually stirred, and processed with a conventional rotary-die process, to obtain soft chewable gelatin capsules of 1850 mg each.
The soft gelatin capsules are then dried at 20°C and 20% relative humidity for five days.
Example 10 The Complex of paroxetine and Copolymer of methacrylic acid and methyl metacrylate (CPC), was obtained by mixing a solution of 3g of Copolymer (Eudragit L) in 150 ml of ethanol with a solution of 3 g of paroxetine base in 100ml of diethyl ether and stirring at room temperature for 12 hours. The solvent was then evaporated under vacuum and the residue was triturated with acetone. The precipitate was collected by suction filtration, washed with acetone and dried. The 4.6 g of CPC gave the following analytical results.
Appearance white powder Bitter taste absent Melting point 215-230°C Paroxetine (HPLC assay) 42.50mg/100mg of CPC Loss on drying 0.4% Example 11
The Complex of paroxetine and Copolymer of methacrylic acid and methyl methacrylate (CPC), was obtained by adding lOg of paroxetine hydrochloride hemihydrate, lOg of Copolimer (Eudragit L) and 2.3g of sodium hydrogen carbonate to 300 ml of water. The mixture was stirred at room temperature for 12 hours, heated to 60°C and stirred at 60°C for 12 hours. After cooling to room temperature, the precipitate was collected by suction filtration, washed with water and dried.
The 18 g of CPC gave the following analytical results.
Appearance off-white powder Bitter taste absent Melting point 195-235°C Paroxetine (HPLC assay) 43.53mg/100mg of CPC Moisture (K.F) 6.3%
Chewable tablets
Examples 12, 13 & 14
Example No.
12 13 14
Complex of paroxetine and Copolymer of methacrylic acid and methyl methacrylate (CPC) (g) 23 46 69
Pregelatinized starch (g) 5 10 15 Aspartame (g) 10 10 10 Strawberry dry flavour (g) 50 50 50 Sorbitol (g) 409 381 353 Magnesium stearate (g) 3 3 3
CDC and pregelatinized starch are mixed, wetted with purified water, kneeded, granulated and then dried at about 40°C. The dried granules are mixed with sorbitol, lactose, saccharin sodium, ammonium glycyrrhizinate, mint dried aroma and magnesium stearate, then the final mixture is pressed into tablets of 150 mg, 300 mg or 600 mg. Bioequivalence Studies
In a cross-over single dose study on 12 healthy volunteers, chewable tablets 50 mg (corresponding to 100 mg of complexed dimenhydrinate were demonstrated to be bio-equivalent to swallow soft gelatin capsules (50 mg) of non-complexed dimenhydrinate product.

Claims

Claims
1. A chewable taste masked formulation comprising a therapeutic agent (or drug) containing at least one basic group or atom optionally in the form of a salt which is reacted with a polymer containing at least one acidic group to form a complex.
2. A chewable taste masked formulation according to claim 1 in which the therapeutic agent is dimenhydrinate or paroxetine.
3. A chewable taste masked formulation according to claim 1 in which the therapeutic agent is in the form of the hydrochloride hemi-hydrate of paroxetine.
4. A chewable taste masked formulation according to claim 1 to 3 in which the polymer is Eudragit.
5. A chewable taste masked formulation accoding to claim 1 to 4 in which the weight ratio of therapeutic agent to drug is 1:0.8 to 1:1.5.
6. A chewable taste masked formulation according to claim 1 to 5 in which the complex of therapeutic agent and polymer is formulated into chewable tablets, candies, chewing gums, or soft chewable gelatin capsules.
7. A chewable taste masked formulation according to claim 6 in which the polymer complex is in the form of chewing gums or chewable tablets.
PCT/EP1994/003903 1993-12-03 1994-11-24 Taste masked composition containing a drug/polymer complex WO1995015155A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU12198/95A AU693144B2 (en) 1993-12-03 1994-11-24 Taste masked composition containing a drug/polymer complex
JP7515376A JPH09505818A (en) 1993-12-03 1994-11-24 Flavor-masked composition containing drug / polymer complex
NZ277238A NZ277238A (en) 1993-12-03 1994-11-24 Taste masked composition containing paroxetine complexed with a polymer
EP95903281A EP0804168A1 (en) 1993-12-03 1994-11-24 Taste masked composition containing a drug/polymer complex

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI93A002540 1993-12-03
ITMI932540A IT1274241B (en) 1993-12-03 1993-12-03 THERAPEUTIC AGENT / POLYMER MATRIX COMPLEXES EQUIPPED WITH IMPROVED FLAVOR CHARACTERISTICS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Publications (1)

Publication Number Publication Date
WO1995015155A1 true WO1995015155A1 (en) 1995-06-08

Family

ID=11367288

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1994/003903 WO1995015155A1 (en) 1993-12-03 1994-11-24 Taste masked composition containing a drug/polymer complex

Country Status (9)

Country Link
EP (1) EP0804168A1 (en)
JP (1) JPH09505818A (en)
CN (1) CN1145586A (en)
AU (1) AU693144B2 (en)
CA (1) CA2177721A1 (en)
IT (1) IT1274241B (en)
NZ (1) NZ277238A (en)
WO (1) WO1995015155A1 (en)
ZA (1) ZA949567B (en)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997003670A1 (en) * 1995-07-20 1997-02-06 Smithkline Beecham P.L.C. Paroxetine controlled release compositions
EP0810224A1 (en) * 1996-05-30 1997-12-03 Asahi Glass Company Ltd. Method of producing amorphous paroxetine hydrochloride
WO1998005360A2 (en) * 1996-08-01 1998-02-12 Basf Aktiengesellschaft Use of (meth)acrylic acid copolymers to increase the permeability of mucous membranes
US5874447A (en) * 1997-06-10 1999-02-23 Synthon B. V. 4-Phenylpiperidine compounds for treating depression
WO1999016440A1 (en) * 1997-09-30 1999-04-08 Pentech Pharmaceuticals, Inc. Amorphous paroxetine composition
US5955475A (en) * 1997-06-30 1999-09-21 Endo Pharmaceuticals Inc. Process for manufacturing paroxetine solid dispersions
WO1999047172A2 (en) * 1998-03-13 1999-09-23 Recordati S.A. Chemical And Pharmaceutical Company Oral pharmaceutical compositions to be taken without liquids, which contain inclusion complexes
US5965555A (en) * 1996-06-07 1999-10-12 Hoechst Aktiengesellschaft Xanthine compounds having terminally animated alkynol side chains
US6063927A (en) * 1998-07-02 2000-05-16 Smithkline Beecham Plc Paroxetine derivatives
AU748804B2 (en) * 1995-07-20 2002-06-13 Smithkline Beecham Plc Paroxetine controlled release compositions
WO2003013529A1 (en) * 2001-08-09 2003-02-20 Smithkline Beecham Plc. Paroxetine glycyrrhizinate
US6548084B2 (en) 1995-07-20 2003-04-15 Smithkline Beecham Plc Controlled release compositions
US6596309B2 (en) 1999-03-12 2003-07-22 Basf Aktiengesellschaft Stable pharmaceutical dosage form for paroxetin anhydrate
US20040242497A1 (en) * 2001-08-09 2004-12-02 Barges Causeret Nathalie Claude Marianne Composition comprising paroxetine and a pharmaceutically acceptable glycyrrhizinate salt
WO2013060343A1 (en) * 2011-10-25 2013-05-02 Expermed S.A. Sublingual pharmaceutical composition containing an antihistamine agent and method for the preparation thereof

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100775154B1 (en) * 1997-12-19 2007-11-12 스미스클라인 비참 코포레이션 Process for Manufacturing Bite-Dispersion Tablets

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0212641A2 (en) * 1985-08-26 1987-03-04 The Procter & Gamble Company Taste masking compositions

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0212641A2 (en) * 1985-08-26 1987-03-04 The Procter & Gamble Company Taste masking compositions

Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7229640B2 (en) * 1995-07-20 2007-06-12 Smithkline Beecham P.L.C. Paroxetine controlled release compositions
US6548084B2 (en) 1995-07-20 2003-04-15 Smithkline Beecham Plc Controlled release compositions
AU748804B2 (en) * 1995-07-20 2002-06-13 Smithkline Beecham Plc Paroxetine controlled release compositions
CN1117567C (en) * 1995-07-20 2003-08-13 史密丝克莱恩比彻姆有限公司 Paroxetine controlled release compositions
EP1382337A1 (en) * 1995-07-20 2004-01-21 Smithkline Beecham Plc Novel formulation containing paroxetine
WO1997003670A1 (en) * 1995-07-20 1997-02-06 Smithkline Beecham P.L.C. Paroxetine controlled release compositions
EP0810224A1 (en) * 1996-05-30 1997-12-03 Asahi Glass Company Ltd. Method of producing amorphous paroxetine hydrochloride
EP1090918A1 (en) * 1996-05-30 2001-04-11 Asahi Glass Company Ltd. Amorphous paroxetine hydrochloride and method of producing it
US5965555A (en) * 1996-06-07 1999-10-12 Hoechst Aktiengesellschaft Xanthine compounds having terminally animated alkynol side chains
US6555124B1 (en) 1996-08-01 2003-04-29 Basf Aktiengesellschaft Use of (meth)acrylic acid copolymers to increase the permeability of mucous membranes
WO1998005360A3 (en) * 1996-08-01 1998-05-07 Basf Ag Use of (meth)acrylic acid copolymers to increase the permeability of mucous membranes
WO1998005360A2 (en) * 1996-08-01 1998-02-12 Basf Aktiengesellschaft Use of (meth)acrylic acid copolymers to increase the permeability of mucous membranes
US6638948B1 (en) 1996-09-09 2003-10-28 Pentech Pharmaceuticals, Inc. Amorphous paroxetine composition
US7598271B1 (en) 1997-06-10 2009-10-06 Noven Therapeutics, Llc Crystalline paroxetine methane sulfonate
US5874447A (en) * 1997-06-10 1999-02-23 Synthon B. V. 4-Phenylpiperidine compounds for treating depression
US6900327B2 (en) 1997-06-10 2005-05-31 Synthon Bct Technologies, Llc 4-phenylpiperidine compounds
EP0991408A1 (en) * 1997-06-30 2000-04-12 Endo Pharmaceuticals Inc. Novel process for manufacturing paroxetine solid dispersions
EP0991408A4 (en) * 1997-06-30 2003-07-09 Endo Pharmaceuticals Inc Novel process for manufacturing paroxetine solid dispersions
US5955475A (en) * 1997-06-30 1999-09-21 Endo Pharmaceuticals Inc. Process for manufacturing paroxetine solid dispersions
WO1999016440A1 (en) * 1997-09-30 1999-04-08 Pentech Pharmaceuticals, Inc. Amorphous paroxetine composition
WO1999047172A2 (en) * 1998-03-13 1999-09-23 Recordati S.A. Chemical And Pharmaceutical Company Oral pharmaceutical compositions to be taken without liquids, which contain inclusion complexes
WO1999047172A3 (en) * 1998-03-13 1999-11-11 Recordati Chem Pharm Oral pharmaceutical compositions to be taken without liquids, which contain inclusion complexes
US6063927A (en) * 1998-07-02 2000-05-16 Smithkline Beecham Plc Paroxetine derivatives
US6596309B2 (en) 1999-03-12 2003-07-22 Basf Aktiengesellschaft Stable pharmaceutical dosage form for paroxetin anhydrate
US20040242497A1 (en) * 2001-08-09 2004-12-02 Barges Causeret Nathalie Claude Marianne Composition comprising paroxetine and a pharmaceutically acceptable glycyrrhizinate salt
WO2003013529A1 (en) * 2001-08-09 2003-02-20 Smithkline Beecham Plc. Paroxetine glycyrrhizinate
WO2013060343A1 (en) * 2011-10-25 2013-05-02 Expermed S.A. Sublingual pharmaceutical composition containing an antihistamine agent and method for the preparation thereof
US20140235656A1 (en) * 2011-10-25 2014-08-21 Expermed S.A. Sublingual pharmaceutical composition containing an antihistamine agent and method for the preparation thereof
AU2011379627B2 (en) * 2011-10-25 2015-09-10 Expermed S.A. Sublingual pharmaceutical composition containing an antihistamine agent and method for the preparation thereof
US9675551B2 (en) 2011-10-25 2017-06-13 Expermed S.A. Sublingual pharmaceutical composition containing an antihistamine agent and method for the preparation thereof

Also Published As

Publication number Publication date
NZ277238A (en) 1998-04-27
AU693144B2 (en) 1998-06-25
EP0804168A1 (en) 1997-11-05
CA2177721A1 (en) 1995-06-08
JPH09505818A (en) 1997-06-10
ITMI932540A1 (en) 1995-06-03
ITMI932540A0 (en) 1993-12-03
ZA949567B (en) 1995-10-10
CN1145586A (en) 1997-03-19
AU1219895A (en) 1995-06-19
IT1274241B (en) 1997-07-15

Similar Documents

Publication Publication Date Title
US4814354A (en) Lipid regulating agents
KR870001960B1 (en) Process for preparing piroxicam compound
CA1288350C (en) Controlled release dihydrocodeine composition
EP1370247B1 (en) Taste masked pharmaceutical compositions
EP0804168A1 (en) Taste masked composition containing a drug/polymer complex
US8993599B2 (en) Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
TWI398273B (en) Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
SE453797B (en) THERAPEUTIC, SOLID UNIT DOSAGE FORM WITH EXTENDED DISPOSAL SAMPLES WHERE BERARM MATERIALS INCLUDE HYDROXYPROPYLMETHYL CELLULOSA WITH HIGH MOLECULES WEIGHT
CA2619438A1 (en) Amorphous solid dispersions of 7-chloro-n,n, 5-trimethyl-4-oxo-3-phenyl-3, 5,-dihydro-4h-pyridazino(4,5-b) indole-1-acetamide
JP2005247874A (en) Process for preparation of oral solid dosage form containing diclofenac
US7229980B2 (en) Paroxetine cholate or cholic acid derivative salts, and composition comprising paroxetine and cholic acid or derivative thereof
WO2007086846A1 (en) Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
RU2240784C1 (en) Arbidol-base medicinal agent
JPS63152321A (en) Lipid regulating composition
US5560921A (en) Chewable decongestant compositions
CA2136946C (en) Oral decongestant product
JP4719899B2 (en) Orally rapidly disintegrating tablets
HU204997B (en) Process for producing carrier system suitable for ensuring controlled biological access to dihydropyridines, as well as new oral dosage form ensuring improved biological access
JP2813792B2 (en) Preparation for oral administration of irsogladine maleate and its production method
RU2276982C2 (en) Agent possessing with anti-inflammatory, analgesic and antipyretic effect as tablet
JPS62190126A (en) Mixed composition of diflunisal and tromethamine
JPH0564126B2 (en)
JPS63310829A (en) Mixture of diflunisal and tromethamine
Jaimini et al. Research Journal of Pharmaceutical, Biological and Chemical Sciences
HU191851B (en) Process for producing of diurethical blood-pressure decreasing combinated medical preparates

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 94194885.4

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AM AT AU BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GE HU JP KE KG KP KR KZ LK LR LT LU LV MD MG MN MW NL NO NZ PL PT RO RU SD SE SI SK TJ TT UA US UZ VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): KE MW SD SZ AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 277238

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 2177721

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 1995903281

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

ENP Entry into the national phase

Ref document number: 1996 652524

Country of ref document: US

Date of ref document: 19961206

Kind code of ref document: A

WWP Wipo information: published in national office

Ref document number: 1995903281

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1995903281

Country of ref document: EP